Recently, ERbeta was demonstrated to inhibit androgen receptor signaling in the prostate and thus is likely to play a pivotal role in the regulation of prostate growth and differentiation. The objective of this proposal is to elucidate the role of ERbeta in androgen-responsive prostate cell models. To do this, ERbeta-interacting proteins will be identified using a T7 phage display system. Following the validation of these protein-protein interactions, we propose to determine the role of these proteins in modulating the physiological and pharmacological actions of ERbeta in androgen-mediated prostate growth mechanisms. To accomplish this, we propose the following specific aims: Aim 1. Identification of factors that interact with ERbeta-ligand complexes in androgen-responsive prostate model cell lines. Aim 2. Validation and characterization of ERbeta-interacting proteins in mammalian cells. Aim 3. Evaluation of the biological consequences of differential ERbeta-cofactor recruitment in androgen-responsive prostate cell lines.